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VIDEO: Novel therapy safe, effective in acute, severe alcoholic hepatitis

BOSTON — In this exclusive video from The Liver Meeting 2019, Tarek Hassanein, MD, FAASLD, professor of medicine at UC San Diego Health and medical director of Southern California GI and Liver Centers, discusses results of a phase 2a study, which demonstrated that DUR-928 was well-tolerated and effective in patients with acute alcoholic hepatitis.

“We are seeing more and more patients coming to us with an acute insult to the liver from alcohol,” Hassanein told Healio Gastroenterology and Liver Disease. “Alcohol use disorders can present in many ways; alcoholic steatosis, alcoholic steatohepatitis, but the form of acute alcoholic hepatitis is very important for us for a very specific reason, it’s mortality is significantly high.”

Hassanein continued and noted that those patients tend to be younger individuals who binge drink and arrive to hospital with rapid deterioration in liver function. Those patients, according to Hassanein, also tend to present with severe jaundice, cholestasis, and then go into multi-organ failure and subsequently die rather quickly.

As a result, the researchers aimed to assess the safety and efficacy of DUR-928 (DURECT), an endogenous sulfated oxysterol, in patients with alcoholic hepatitis, as well as severe alcoholic hepatitis.

The open-label, phase 2a multicenter trial comprised 19 patients, of whom 15 had Maddrey’s Discriminant Function of 32 or higher, 12 had MELD scores of 21 to 30 and 11 had baseline serum bilirubin levels of 8 mg/dL or more.

All patients received DUR-928 at 30, 90, or 150 mg intravenously on day 1 and day 4 if they were still hospitalized and were followed for 28 days.

All the patients survived through the follow-up period. Eighty-nine percent of patients (Lille score < 0.45) who received DUR-928 were deemed treatment responders. Among the 15 patients with severe alcoholic hepatitis (DF 32), 87% responded to treatment.

All patients with severe alcoholic hepatitis who received 30 mg or 90 mg of DUR-928 (n = 11) responded to treatment.

MELD scores at day 28 follow-up were significantly reduced from baseline in patients with severe alcoholic hepatitis (–17.5%, P = .01).

There were no serious adverse events related to the study drug.

“For the first time, we start to see some new molecule that can help patients with acute alcoholic hepatitis,” Hassanein said. “With the success that we have seen, [it] dictates the importance of expanding that experience in [a] much larger number of a population with a very specific description of how bad is their acute alcoholic hepatitis and go to a larger study.” – by Ryan McDonald

Reference: Hassanein T, et al. Abstract LO9. Presented at: The Liver Meeting; Nov. 7-12, 2019; Boston.

Disclosure: Hassanein reports receiving grant/research support from Assembly Biosciences and DURECT.

BOSTON — In this exclusive video from The Liver Meeting 2019, Tarek Hassanein, MD, FAASLD, professor of medicine at UC San Diego Health and medical director of Southern California GI and Liver Centers, discusses results of a phase 2a study, which demonstrated that DUR-928 was well-tolerated and effective in patients with acute alcoholic hepatitis.

“We are seeing more and more patients coming to us with an acute insult to the liver from alcohol,” Hassanein told Healio Gastroenterology and Liver Disease. “Alcohol use disorders can present in many ways; alcoholic steatosis, alcoholic steatohepatitis, but the form of acute alcoholic hepatitis is very important for us for a very specific reason, it’s mortality is significantly high.”

Hassanein continued and noted that those patients tend to be younger individuals who binge drink and arrive to hospital with rapid deterioration in liver function. Those patients, according to Hassanein, also tend to present with severe jaundice, cholestasis, and then go into multi-organ failure and subsequently die rather quickly.

As a result, the researchers aimed to assess the safety and efficacy of DUR-928 (DURECT), an endogenous sulfated oxysterol, in patients with alcoholic hepatitis, as well as severe alcoholic hepatitis.

The open-label, phase 2a multicenter trial comprised 19 patients, of whom 15 had Maddrey’s Discriminant Function of 32 or higher, 12 had MELD scores of 21 to 30 and 11 had baseline serum bilirubin levels of 8 mg/dL or more.

All patients received DUR-928 at 30, 90, or 150 mg intravenously on day 1 and day 4 if they were still hospitalized and were followed for 28 days.

All the patients survived through the follow-up period. Eighty-nine percent of patients (Lille score < 0.45) who received DUR-928 were deemed treatment responders. Among the 15 patients with severe alcoholic hepatitis (DF 32), 87% responded to treatment.

All patients with severe alcoholic hepatitis who received 30 mg or 90 mg of DUR-928 (n = 11) responded to treatment.

MELD scores at day 28 follow-up were significantly reduced from baseline in patients with severe alcoholic hepatitis (–17.5%, P = .01).

There were no serious adverse events related to the study drug.

“For the first time, we start to see some new molecule that can help patients with acute alcoholic hepatitis,” Hassanein said. “With the success that we have seen, [it] dictates the importance of expanding that experience in [a] much larger number of a population with a very specific description of how bad is their acute alcoholic hepatitis and go to a larger study.” – by Ryan McDonald

Reference: Hassanein T, et al. Abstract LO9. Presented at: The Liver Meeting; Nov. 7-12, 2019; Boston.

Disclosure: Hassanein reports receiving grant/research support from Assembly Biosciences and DURECT.

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